A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)

NCT04374136 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: AL001-3
• Study Type: interventional
• Target: 119
• Locations: 16 countries
• Sites: 44

Brief Summary

A phase 3 double blind, placebo controlled study evaluating the efficacy and safety of AL001 in participants at risk for or with frontotemporal dementia due to heterozygous mutations in the progranulin gene.

Conditions

Frontotemporal Dementia

Outcome Measures

Primary Outcomes (1)

• Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB

  The Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer's Disease Coordinating Center frontotemporal lobar degeneration Behavior \& Language Domains Sum of Boxes (CDR® plus NACC FTLD-SB) is administered by a healthcare professional and based on individual ratings of the eight domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care, language and behavior. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 8 individual domain ratings, or "box scores", were added together to give the CDR® plus NACC FTLD-SB which ranges from 0-24. Higher score indicates severe impairment.

  Through study completion, on average up to 96 weeks

Secondary Outcomes (5)

• Change in Clinical Global Impression-Severity (CGI-S) Score

  Baseline to 96 weeks

• Change in Clinical Global Impression-Improvement (CGI-I) Score

  Baseline to 96 weeks

• Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score

  Baseline to 96 weeks

• Pharmacodynamic Biomarkers

  Baseline to 96 weeks

• Evaluation of safety and tolerability of AL001: Incidence of adverse events

  Baseline to 96 weeks

Other Outcomes (1)

• Optional Open-Label Extension

  96 weeks

Study Arms (3)

AL001

EXPERIMENTAL

AL001 every 4 weeks

Drug: AL001

Placebo

PLACEBO COMPARATOR

Placebo every 4 weeks

Drug: Placebo

Open label - AL001

EXPERIMENTAL

AL001 every 4 weeks

Drug: Open label - AL001

Interventions

AL001 DRUG

Administered via intravenous (IV) infusion

AL001

Open label - AL001 DRUG

Administered via intravenous (IV) infusion

Open label - AL001

Placebo DRUG

Administered via intravenous (IV) infusion

Placebo

Eligibility Criteria

• Age: 25 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persons with a progranulin gene mutation and at risk of developing FTD symptoms as evidenced by a biomarker, or persons with a progranulin gene mutation and diagnosed with FTD.
• If symptomatic, one or more of the criteria for the diagnosis of possible behavioral variant FTD, or a diagnosis of Primary Progressive Aphasia.
• Study partner who consents to study participation and who cares for/visits the participant daily for at least 5 hours per week.
• Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).

You may not qualify if:

• Dementia due to a condition other than FTD including, but not limited to, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, Huntington disease, or vascular dementia.
• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
• Current uncontrolled hypertension, diabetes mellitus or thyroid disease. Clinically significant heart disease, liver disease or kidney disease. History or evidence of clinically significant brain disease other than FTD.
• Females who are pregnant or breastfeeding, or planning to conceive within the study period.
• Any experimental vaccine or gene therapy.
• History of cancer within the last 5 years.
• Current use of anticoagulant medications (e.g., coumadin, heparinoids, apixaban).
• Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care.

Sponsors & Collaborators

• Alector Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (44)

Dignity Health

Phoenix, Arizona, 85013, United States

Location

University of California San Diego

La Jolla, California, 92093-0648, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Mayo Comprehensive Cancer Center - PPDS

Rochester, Minnesota, 55905, United States

Location

Irving Institute for Clinical and Translational Research

New York, New York, 10032, United States

Location

University Of Cincinnati Gardner Neuroscience institute

Cincinnati, Ohio, 45219, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Houston Methodist Institute for Academic Medicine

Houston, Texas, 77030, United States

Location

Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia

Buenos Aires, 2325, Argentina

Location

Box Hill Hospital

Box Hill, 3128, Australia

Location

The Queen Elizabeth Hospital

Woodville, Australia

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

The University of Western Ontario

London, Canada

Location

Sunnybrook Research Institute - University of Toronto

Toronto, Canada

Location

CHU de Bordeaux

Bordeaux, France

Location

CHRU Lille

Lille, France

Location

Groupe Hospitalier Pitié Salpétrière

Paris, France

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Eginitio University General Hospital of Athens - 1st University Neurology Clinic

Athens, Attica, 115 28, Greece

Location

University General Hospital of Alexandroupolis - Department of Neurology

Alexandroupoli, Evros, 68100, Greece

Location

Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara

Baggiovara, Italy

Location

ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia

Brescia, Italy

Location

IRCCS - Centro S. Giovanni di Dio Fatebenefratelli

Brescia, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta

Milan, Italy

Location

PIA Fondazione Panico

Tricase, Italy

Location

Erasmus MC

Rotterdam, Netherlands

Location

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, Portugal

Location

Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital CUF Descobertas

Lisbon, Portugal

Location

Centro Hospitalar do Porto - Hospital de Santo António

Porto, 4099-001, Portugal

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitario de Donostia

Donostia / San Sebastian, Spain

Location

Karolinska Universitetssjukhuset Huddinge - PPDS

Huddinge, Sweden

Location

Felix Platter Spital

Basel, Switzerland

Location

Istanbul University Medical Faculty

Istanbul, Fatih, 34093, Turkey (Türkiye)

Location

University College London

London, United Kingdom

Location

MeSH Terms

Conditions

Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• TBD TBD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: May 5, 2020
• Study Start: July 23, 2020
• Primary Completion: September 1, 2025
• Study Completion: January 6, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

GR (2); IT (6); CH (1); TU (1); CA (2); SE (1); AU (2); PT (4); ES (2); BE (1); DE (2); NL (1); AR (1); US (14); FR (3); GB (1)